1. Field of the Invention
The present invention relates to the design and use of a novel scanning magnetic imaging method with high resolution and long detection range.
2. Background
Magnetic nanoparticles are widely used as biochemical markers, drug-delivery carriers and imaging contrast agents. Moreover, micrometer- and nanometer-sized particles are commonly used in biochemical assays as a means to capture, concentrate, and manipulate target analytes and increasingly so as detection labels for assay readout. These detection applications benefit from the relatively large magnetic field signature generated by the beads when magnetized by an applied magnetic field, and from the very low incidence of background magnetic signals. These features altogether make magnetic detection an attractive technology for a range of biochemical analysis.
However, the precise determination of the position and number of particles at a given time is vital for these purposes. In many applications, such as assay analysis on microchips and in vivo imaging, the magnetic particles are far from the detectors, on the order of several millimeters to a few centimeters. This makes it challenging to obtain desired spatial information and sufficient detection limit because of the r−3 dependence of magnetic field strength, where r is the distance between the sample and the detector.
Successful imaging of magnetic nanoparticles in practical settings requires two criteria. One is high sensitivity in directly detecting magnetic fields. The other is the capability of resolving spatial information at a long detection distance. Various magnetic force microscopy and magnetic resonance force microscopy techniques, which usually have a detection range of around a few nanometers or less, are thus not suitable for those applications. Similarly, room-temperature giant magneto-resistive sensors are only applicable when the sensor is placed within a few micrometers of the sample. Large-scale magnetic imaging modalities often lack sensitivity because of the distance dependence of the magnetic field and magnetic response; the degraded sensitivity requires the use of impractical amounts of sample. Indirect detection of magnetic particles has also been investigated. Optical detection offers high sensitivity, but it requires a transparent environment, which cannot be satisfied in many cases. Separately, conventional magnetic resonance imaging offers high spatial resolution via encoding with gradient magnetic fields, but with drawbacks including poor sensitivity to dc magnetic field and the requirement of a superconducting magnet.
Atomic magnetometers have also been used to detect magnetic particles; however, no spatial information was extracted, nor could the amount of the sample be determined. Since magnetic field is a function of both the number of nanoparticles and their distance to the detector, it is difficult to resolve spatial information without prior knowledge of the amount of the sample.
A similar situation is encountered during imaging of biological magnetic fields, for example, the magnetic fields from human brain or heart. The magnetic field strength is determined by both the amplitude of the magnetic source and its distance to the detectors. With one measurement or a few measurements, it is difficult to simultaneously localize the source of the magnetic field and reveal its strength.
It is therefore the purpose of the present invention to develop a scanning imaging method to generate a two-dimensional or three-dimensional map of the magnetic fields.